Acylation. Part XVIII. The kinetics and mechanisms of the reactions of dimethylketen, isobutyric anhydride, and isobutyryl halides with anilines in ether

Abstract

The spontaneous acylation of substituted anilines by dimethylketen in ether solution follows the equation -d[keten]/dt={k₁[aniline]+k₂[aniline]²}[keten]=k_obs[keten]. Two paths are therefore involved, in one of which a second aniline molecule has a catalytic role. The effect of temperature on k₂ is compatible with the participation of dimeric aniline in this step. At 25°, the rate constants k₁ and k₂ are related to the base strength of the aniline as log k₁=- 0·70 log K_a- 2·95 and log k₂=- 1·20 log K_a- 3·90, where K_a is the dissociation constant of the corresponding anilinium ion in water. The form of the results is similar to that found for acylation by diphenylketen in benzene. Assuming the solvent has no effect on the reaction velocity, values of k₁ show diphenylketen to be ca. 10-fold more reactive towards a given aniline than dimethylketen. The acylation by dimethylketen is powerfully catalysed by carboxylic acids. The catalysed reaction is first-order in each reactant, and the catalytic effect of an acid is not related to acid strength. There are reasons for suspecting a cyclic transition state in this reaction, which does not proceed through the anhydride as intermediate. Acylation of anilines by isobutyric anhydride in ether is catalysed by the isobutyric acid produced. The acid-catalysed path is first-order in anhydride, aniline, and catalyst. The spontaneous, bimolecular reaction between aniline and anhydride is very slow, and the acid-catalysed route is not as rapid as the analogous process involving the keten, although the catalytic enhancement of the spontaneous rate is relatively much the same. In the anhydride reaction the catalyst probably assists the departure of the leaving group. Acylation of anilines by isobutyryl chloride or bromide in ether is first-order in each reactant. Towards m-chloroaniline the bromide is ca. 30-fold more reactive than the chloride, which is ca. 4·5-fold more reactive than dimethylketen in the comparable uncatalysed process (k₁). The acylation by acylhalides is not catalysed by the hydrogen halide produced, nor by added carboxylic acid. The most effective method for isobutyrylation studied here is the combination dimethylketen plus carboxylic acid catalyst.